DOI QR코드

DOI QR Code

OASL1 Traps Viral RNAs in Stress Granules to Promote Antiviral Responses

  • Kang, Ji-Seon (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Hwang, Yune-Sahng (Department for Integrated OMICs for Biomedical Science, Yonsei University) ;
  • Kim, Lark Kyun (Severance Biomedical Science Institute and BK21 PLUS project to Medical Sciences, Gangnam Severance Hospital, Yonsei University College of Medicine) ;
  • Lee, Sujung (Department of Integrative Bioscience and Biotechnology, College of Life Sciences, Sejong University) ;
  • Lee, Wook-Bin (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Kim-Ha, Jeongsil (Department of Integrative Bioscience and Biotechnology, College of Life Sciences, Sejong University) ;
  • Kim, Young-Joon (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University)
  • Received : 2017.11.08
  • Accepted : 2017.12.17
  • Published : 2018.03.31

Abstract

Oligoadenylate synthetase (OAS) protein family is the major interferon (IFN)-stimulated genes responsible for the activation of RNase L pathway upon viral infection. OAS-like (OASL) is also required for inhibition of viral growth in human cells, but the loss of one of its mouse homolog, OASL1, causes a severe defect in termination of type I interferon production. To further investigate the antiviral activity of OASL1, we examined its subcellular localization and regulatory roles in IFN production in the early and late stages of viral infection. We found OASL1, but not OASL2, formed stress granules trapping viral RNAs and promoted efficient RLR signaling in early stages of infection. Stress granule formation was dependent on RNA binding activity of OASL1. But in the late stages of infection, OASL1 interacted with IRF7 transcripts to inhibit translation resulting in down regulation of IFN production. These results implicate that OASL1 plays context dependent functions in the antiviral response for the clearance and resolution of viral infections.

Acknowledgement

Supported by : NRF

References

  1. Arimoto, K., Fukuda, H., Imajoh-Ohmi, S., Saito, H., and Takekawa, M. (2008). Formation of stress granules inhibits apoptosis by suppressing stress-responsive MAPK pathways. Nat. Cell Biol. 10, 1324-1332. https://doi.org/10.1038/ncb1791
  2. Bruns, A.M., and Horvath, C.M. (2015). LGP2 synergy with MDA5 in RLR-mediated RNA recognition and antiviral signaling. Cytokine 74, 198-206. https://doi.org/10.1016/j.cyto.2015.02.010
  3. Buchan, J.R., Kolaitis, R.-M., Taylor, J.P., and Parker, R. (2013). Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function. Cell 153, 1461-1474. https://doi.org/10.1016/j.cell.2013.05.037
  4. Chernov, K.G., Barbet, A., Hamon, L., Ovchinnikov, L.P., Curmi, P.A., and Pastre, D. (2009). Role of microtubules in stress granule assembly: microtubule dynamical instability favors the formation of micrometric stress granules in cells. J. Biol. Chem. 284, 36569-36580. https://doi.org/10.1074/jbc.M109.042879
  5. Choi, B.Y., Sim, C.K., Cho, Y.S., Sohn, M., Kim, Y.-J., Lee, M.S., and Suh, S.W. (2016). 2′-5′ oligoadenylate synthetase-like 1 (OASL1) deficiency suppresses central nervous system damage in a murine MOG-induced multiple sclerosis model. Neurosci. Lett. 628, 78-84. https://doi.org/10.1016/j.neulet.2016.06.026
  6. Dhar, J., Cuevas, R.A., Goswami, R., Zhu, J., Sarkar, S.N., and Barik, S. (2015). 2′-5′-oligoadenylate synthetase-like protein inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1. J. Virol. 89, 10115-10119. https://doi.org/10.1128/JVI.01076-15
  7. Dixit, E., Boulant, S., Zhang, Y., Lee, A.S.Y., Odendall, C., Shum, B., Hacohen, N., Chen, Z.J., Whelan, S.P., Fransen, M., et al. (2010). Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141, 668-681. https://doi.org/10.1016/j.cell.2010.04.018
  8. Eskildsen, S., Hartmann, R., Kjeldgaard, N.O., and Justesen, J. (2002). Gene structure of the murine 2′-5′-oligoadenylate synthetase family. Cell. Mol. Life Sci. 59, 1212-1222. https://doi.org/10.1007/s00018-002-8499-2
  9. Kato, H., Takeuchi, O., Mikamo- Satoh, E., Hirai, R., Kawai, T., Matsushita, K., Hiiragi, A., Dermody, T.S., Fujita, T., and Akira, S. (2008). Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J. Exp. Med. 205, 1601-1610. https://doi.org/10.1084/jem.20080091
  10. Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K.J., et al. (2006). Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441, 101-105. https://doi.org/10.1038/nature04734
  11. Kedersha, N.L., Gupta, M., Li, W., Miller, I., and Anderson, P. (1999). RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. J. Cell Biol. 147, 1431-1442. https://doi.org/10.1083/jcb.147.7.1431
  12. Kedersha, N., Chen, S., Gilks, N., Li, W., Miller, I.J., Stahl, J., and Anderson, P. (2002). Evidence that ternary complex (eIF2-GTPtRNA(i)(Met))-deficient preinitiation complexes are core constituents of mammalian stress granules. Mol. Biol. Cell 13, 195-210. https://doi.org/10.1091/mbc.01-05-0221
  13. Kedersha, N., Ivanov, P., and Anderson, P. (2013). Stress granules and cell signaling: more than just a passing phase? Trends Biochem. Sci. 38, 494-506. https://doi.org/10.1016/j.tibs.2013.07.004
  14. Kim, J., Lee, J., Lee, S., Lee, B., and Kim-Ha, J. (2014a). Phylogenetic comparison of oskar mRNA localization signals. Biochem. Biophys. Res. Commun. 444, 98-103. https://doi.org/10.1016/j.bbrc.2014.01.021
  15. Kim, Y.-M., Choi, W.Y., Oh, C.-M., Han, G.-H., and Kim, Y.-J. (2014b). Secondary structure of the Irf7 5'-UTR, analyzed using SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension). BMB Rep. 47, 558-562. https://doi.org/10.5483/BMBRep.2014.47.10.281
  16. Langereis, M.A., Feng, Q., and van Kuppeveld, F.J. (2013). MDA5 localizes to stress granules, but this localization is not required for the induction of type I interferon. J. Virol. 87, 6314-6325. https://doi.org/10.1128/JVI.03213-12
  17. Lee, M.S., Kim, B., Oh, G.T., and Kim, Y.-J. (2013a). OASL1 inhibits translation of the type I interferon-regulating transcription factor IRF7. Nat. Immunol. 14, 346-355. https://doi.org/10.1038/ni.2535
  18. Lee, M.S., Park, C.H., Jeong, Y.H., Kim, Y.-J., and Ha, S.-J. (2013b). Negative regulation of type I IFN expression by OASL1 permits chronic viral infection and $CD8^+$ T-cell exhaustion. PLoS Pathog. 9, e1003478. https://doi.org/10.1371/journal.ppat.1003478
  19. Lee, N.-R., Kim, H.-I., Choi, M.-S., Yi, C.-M., and Inn, K.-S. (2015). Regulation of MDA5-MAVS antiviral signaling axis by TRIM25 through TRAF6-mediated $NF-{\kappa}B$ activation. Mol. Cells 38, 759-764. https://doi.org/10.14348/molcells.2015.0047
  20. Loschi, M., Leishman, C.C., Berardone, N., and Boccaccio, G.L. (2009). Dynein and kinesin regulate stress-granule and P-body dynamics. J. Cell. Sci. 122, 3973-3982. https://doi.org/10.1242/jcs.051383
  21. Narita, R., Takahasi, K., Murakami, E., Hirano, E., Yamamoto, S.P., Yoneyama, M., Kato, H., and Fujita, T. (2014). A novel function of human pumilio proteins in cytoplasmic sensing of viral infection. PLoS Pathog. 10, e1004417. https://doi.org/10.1371/journal.ppat.1004417
  22. Oh, J.E., Lee, M.S., Kim, Y.-J., and Lee, H.K. (2016a). OASL1 deficiency promotes antiviral protection against genital herpes simplex virus type 2 infection by enhancing type I interferon production. Sci. Rep. 6, 19089. https://doi.org/10.1038/srep19089
  23. Oh, S.-W., Onomoto, K., Wakimoto, M., Onoguchi, K., Ishidate, F., Fujiwara, T., Yoneyama, M., Kato, H., and Fujita, T. (2016b). Leadercontaining uncapped viral transcript activates RIG-I in antiviral stress granules. PLoS Pathog. 12, e1005444. https://doi.org/10.1371/journal.ppat.1005444
  24. Ohn, T., and Anderson, P. (2010). The role of posttranslational modifications in the assembly of stress granules. Wiley Interdiscip Rev. RNA 1, 486-493. https://doi.org/10.1002/wrna.23
  25. Onomoto, K., Jogi, M., Yoo, J.-S., Narita, R., Morimoto, S., Takemura, A., Sambhara, S., Kawaguchi, A., Osari, S., Nagata, K., et al. (2012). Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity. PLoS ONE 7, e43031. https://doi.org/10.1371/journal.pone.0043031
  26. Park, I.-H., Baek, K.-W., Cho, E.-Y., and Ahn, B.-Y. (2011). PKRdependent mechanisms of interferon-${\alpha}$ for inhibiting hepatitis B virus replication. Mol. Cells 32, 167-172. https://doi.org/10.1007/s10059-011-1059-6
  27. Sim, C.K., Cho, Y.S., Kim, B.S., Baek, I.-J., Kim, Y.-J., and Lee, M.S. (2016). 2′-5′ Oligoadenylate synthetase-like 1 (OASL1) deficiency in mice promotes an effective anti-tumor immune response by enhancing the production of type I interferons. Cancer Immunol. Immunother. 1-13.
  28. Szymanski, M.R., Jezewska, M.J., Bujalowski, P.J., Bussetta, C., Ye, M., Choi, K.H., and Bujalowski, W. (2011). Full-length Dengue virus RNAdependent RNA polymerase-RNA/DNA complexes: stoichiometries, intrinsic affinities, cooperativities, base, and conformational specificities. J. Biol. Chem. 286, 33095-33108. https://doi.org/10.1074/jbc.M111.255034
  29. Triantafilou, K., Vakakis, E., Kar, S., Richer, E., Evans, G.L., and Triantafilou, M. (2012). Visualisation of direct interaction of MDA5 and the dsRNA replicative intermediate form of positive strand RNA viruses. J. Cell. Sci. 125, 4761-4769. https://doi.org/10.1242/jcs.103887
  30. Tsai, N.-P., and Wei, L.-N. (2010). RhoA/ROCK1 signaling regulates stress granule formation and apoptosis. Cell. Signal. 22, 668-675. https://doi.org/10.1016/j.cellsig.2009.12.001
  31. Wack, A., Terczynska-Dyla, E., and Hartmann, R. (2015). Guarding the frontiers: the biology of type III interferons. Nat. Immunol. 16, 802-809. https://doi.org/10.1038/ni.3212
  32. Yoneyama, M., Jogi, M., and Onomoto, K. (2016). Regulation of antiviral innate immune signaling by stress-induced RNA granules. J. Biochem. 159, 279-286.
  33. Yoneyama, M., Onomoto, K., Jogi, M., Akaboshi, T., and Fujita, T. (2015). Viral RNA detection by RIG-I-like receptors. Curr. Opin. Immunol. 32, 48-53. https://doi.org/10.1016/j.coi.2014.12.012
  34. Yoo, J.-S., Takahasi, K., Ng, C.S., Ouda, R., Onomoto, K., Yoneyama, M., Lai, J.C., Lattmann, S., Nagamine, Y., Matsui, T., et al. (2014). DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation. PLoS Pathog. 10, e1004012. https://doi.org/10.1371/journal.ppat.1004012
  35. Zhang, P., Li, Y., Xia, J., He, J., Pu, J., Xie, J., Wu, S., Feng, L., Huang, X., and Zhang, P. (2014). IPS-1 plays an essential role in dsRNAinduced stress granule formation by interacting with PKR and promoting its activation. J. Cell. Sci. 127, 2471-2482. https://doi.org/10.1242/jcs.139626
  36. Zhu, J., Zhang, Y., Ghosh, A., Cuevas, R.A., Forero, A., Dhar, J., Ibsen, M.S., Schmid-Burgk, J.L., Schmidt, T., Ganapathiraju, M.K., et al. (2014). Antiviral activity of human OASL protein is mediated by enhancing signaling of the RIG-I RNA sensor. Immunity 40, 936-948. https://doi.org/10.1016/j.immuni.2014.05.007